Pain-related disorders cause an incalculable toll in human suffering and present a significant economic problem. The development of new treatments for these disorders is being hindered by a lack of information about the basic brain mechanisms that support sensory aspects of pain experience. Functional imaging studies using functional magnetic resonance imaging (fMRI) provide powerful tools for addressing such issues in human subjects. Using such techniques, a highly distributed network of brain regions that may contribute to sensory discriminative pain processes has been identified. However, the involvement of specific components in supporting conscious awareness of discrete dimensions of pain, such as intensity and location, remains poorly understood. These perceived sensory aspects of pain can be dramatically modulated by cognitive interpretation and expectations about the nature of the stimulus. Yet, the brain mechanisms underlying this modulation remain unknown. A series of combined psychophysical and functional imaging studies will systematically test the hypotheses that 1) activation of the frontal cortex is necessary for subjective awareness of pain, 2) distinct parieto-frontal mechanisms are engaged in processes supporting conscious awareness of the location and intensity of painful stimuli, and 3) that activation within these areas can be modulated by internally-maintained contextual information. These studies will significantly enhance our knowledge of basic brain mechanisms underlying the pain experience, while simultaneously providing new directions for behavioral strategies of pain management. PUBLIC HEALTH RELEVANCE Pain afflicts more Americans than heart disease and stroke, diabetes, and cancer combined. Pain exacts an incalculable toll in human suffering and is a tremendous economic problem. The proposed research will focus on understanding the basic mechanisms that support the most clinically important features of pain - intensity and location - in order to provide a solid knowledge base for the development of improved treatments for pain.